Primary Vaginal Adenocarcinoma Research Articles

Primary vulvar and vaginal adenocarcinomas of intestinal-type are closer to colorectal adenocarcinomas than to carcinomas of Müllerian origin

Primary vulvar and vaginal adenocarcinomas of intestinal-type are closer to colorectal adenocarcinomas than to carcinomas of Müllerian origin

Human papilloma virus associated primary vaginal adenocarcinoma

Primary vaginal adenocarcinoma associated with human papillomavirus (HPV) infection is extremely rare. We report a case of primary adenocarcinoma of the vagina associated with human papilloma virus successfully treated with anterior pelvic exenteration and adjuvant concurrent chemoradiation therapy. A 51-year-old postmenopausal woman (gravida 1, para 1) presented with intermittent vaginal bleeding and pelvic pain. She was found to have a 5 × 5 cm necrotic tumor took up the vaginal. She had no previous history of antenatal exposure to diethylstilbestrol (DES). Pelvic magnetic resonance imaging (MRI) demonstrated a 4.8 × 6.0 cm mass in the vaginal canal, an 1.1 × 2.6 cm mass at the urinary bladder dome and a 1.1 cm irregular lymph node at the right external iliac chain with increased fluorodeoxyglucose (FDG) uptake from Fused whole-body positron emission tomography-computed tomography (PET-CT). Based on clinical investigations, the patient was diagnosed with a primary adenocarcinoma of vagina, staged International Fedestration of Gynecology and Obstetrics (FIGO) IVa. Anterior pelvic exenteration, simple vulvectomy, total vaginectomy, both pelvic lymph node dissection, and para-aortic lymph node dissection with ileal conduit urinary diversion (Bricker’s operation) was done. Histologically primary vaginal HPV type 16-associated adenocarcinoma was confirmed. Both obturator lymph node was positive for metastasis. Postoperatively, the patient received weekly cisplatin regimen administered with a dose of 40 mg/m2 on day 1 of external radiation therapy (RT), 1 to 4 hours before RT initiation. External beam pelvic RT dose prescription to the whole pelvis was 59.4 Gy in 33 fractions at the isocenter. But, after total dose of 43.2 Gy, patient complained severe bowel habit change and discontinued further treatment. The patient remains free from recurrence 8 months after initial surgery. In the lack of information and comparative analysis of management options for the more unusual and rare varieties of primary vaginal neoplasms in the literature, this suggests the possibility that surgical treatment may be preferentially selected on a case-by-case basis.

Diagnostic and Therapeutic Approach in a Metastatic Vaginal Adenocarcinoma: A Case Report

BackgroundVaginal adenocarcinomas (VAC) are most often reported after intrauterine exposition to diethylstilbestrol (DES). Rarely, VACs are reported as a malignant transformation of vaginal adenosis or endometriosis, in the context of chromosomal abnormalities or malformations of the uterus or the vagina. VACs without DES exposition have a poor prognosis and a significantly worse outcome compared to vaginal squamous cell carcinomas or DES-associated VACs.ObjectiveHere, we report the case of a primarily metastatic VAC, treated successfully with different lines of chemo-, antiangiogenic, antibody, and immunotherapy.CaseThe 49-year-old patient presented in 5/2018 with a primarily pulmonary metastatic VAC. Significant tumor reduction was seen after six cycles of carboplatin AUC5/paclitaxel 175 mg/m²/bevacizumab 15 mg/kg q3w. Bevacizumab maintenance therapy and later cisplatin mono 50 mg/m² q2w led to local and distant tumor progression. To identify a potential targeted therapy, new tumor biopsies were obtained. Immunohistochemistry revealed ERBB2 expression, and paclitaxel 80 mg/m² weekly plus trastuzumab 4 mg/m² respectively 2 mg/m² q3w was administered. Due to local and pulmonal tumor progression after 6 months and persistent ERBB2 positivity, the therapy was adjusted to trastuzumab emtansine (T-DM1) 3.6 mg/kg q3w; however, the patient remained locally progressive after three cycles of T-DM1 and additionally showed a new bone metastasis. The new tumor biopsies revealed a combined positive score (CPS) of 2 regarding PD-L1, and pembrolizumab 200 mg q3w was initiated. The bone metastasis was radiated and treated with denosumab 120 mg q4w. Extreme tumor regression followed by stable disease was maintained for 9 months. Due to a slow locoregional progress only with new inguinal lymph node and pararectal lymph node metastases, a new tumor biopsy was taken. Molecular profiling showed an ARID1A mutation, a mutational burden of 5.1 mutations per megabase, and no genfusions. Based on these findings, therapy with PD-L1 antibodies, PD-1 antibodies, gemcitabine, or dasatinib was suggested. Therefore, administration of pembrolizumab was continued and local radiation therapy was performed. This led to a decrease in local tumor manifestations and a stable systemic disease.ConclusionOur case demonstrates the diagnostic and therapeutic approach in a patient with primary metastatic vaginal adenocarcinoma. By tumorgenetic profiling, different lines of systemic therapy, namely, antiangiogenic therapy, monoclonal antibody therapy, immunotherapy, and local radiation therapy, were identified and successfully administered.

Intestinal-type primary vaginal adenocarcinoma. Review of the literature with report of a case: from diagnosis to management

Intestinal-type primary vaginal adenocarcinoma. Review of the literature with report of a case: from diagnosis to management

A novel group of HPV-related adenocarcinomas of the lower anogenital tract (vagina, vulva, and anorectum) in women and men resembling HPV-related endocervical adenocarcinomas.

Human papillomavirus (HPV) is an oncogenic virus associated with the development of several human cancers. Primary vaginal, vulvar, and anal adenocarcinomas are rare and, to date, have rarely been shown to be associated with HPV infection. We report a series of nine HPV-related adenocarcinomas of the lower anogenital tract distal to the cervix. The tumors involved the vagina (4), anorectum (3), and vulva (2). Two of the three anorectal cases involved men. Patients presented with a vulvar or vaginal mass/nodule, painless rectal bleeding, or during screening colonoscopy. Lesions ranged in size from 3.2 to 8.4 cm. The most salient morphologic characteristic was the presence of papillary or villiform/villoglandular architecture in all cases. Tumors displayed features similar to those of usual type high-risk HPV-related endocervical adenocarcinoma, namely, mucinous or mucin-poor (pseudoendometrioid) features or a hybrid of these, with columnar cells with crowded, cigar-shaped to ovoid irregular nuclei. Mitoses (mostly apical) and apoptotic bodies were easily identified. Adenosis was present in two vaginal cases. One anal tumor featured abundant intracytoplasmic mucin that was multivacuolated in some areas imparting a "clear cell"-like appearance. All tumors were diffusely and strongly positive for p16. Seven of seven tested cases were positive for high-risk HPV by in situ hybridization or polymerase chain reaction. Follow-up information, available in five patients, revealed two local recurrences but no tumor related deaths or distant metastases. We report the first well-documented series of HPV-associated primary adenocarcinomas of the vagina, vulva, and anorectum and broaden the spectrum of HPV-related neoplasia involving the lower anogenital tract in both women and men.

Primary vaginal adenocarcinoma of intestinal-type: case report of a rare gynaecological tumour.

ABSTRACTVaginal cancer is rare and accounts for only 1 to 2% of all gynaecological malignancies. They arise as primary squamous cell cancers or are the result of extension from the cervix or vulva. Primary mucinous vaginal adenocarcinoma of intestinal-type is an extremely rare malignancy of unknown histogenesis with a diagnostic dilemma for the clinician and histopathologist. We presented the case of a 40-year-old Para 0+2 woman with the complaint of a mass in the vagina and recurrent vaginal bleeding who was evaluated and worked-up for examination under anaesthesia and biopsy of the vaginal mass. The histological examination revealed the unusual intestinal-type variant of adenocarcinoma of the vagina. Recognition of this rare entity is important, particularly to avoid the pitfall of misdiagnosing metastatic disease as primary vaginal cancer.

Expression of Markers of Müllerian Clear Cell Carcinoma in Primary Cervical and Vaginal Gastric-type Adenocarcinomas.

The incidence of cervical adenocarcinoma, both absolute and relative to squamous cell carcinoma, is increasing. Most cervical adenocarcinomas are human papillomavirus associated, although non-human papillomavirus-associated neoplasms exist; the latter include gastric-type adenocarcinoma (GAS) and clear cell carcinoma (CCC). Histologically, these 2 tumors may superficially resemble one other and although morphologic evaluation usually permits a correct diagnosis, immunohistochemistry may be required to resolve diagnostic uncertainty, especially in a small biopsy specimen. Markers of CCC include hepatocyte nuclear factor 1 beta (HNF1β) and Napsin A. In order to explore the utility of these markers in distinguishing between GAS and CCC, we stained 24 cases of GAS (19 cervical, 5 vaginal), 3 of cervical gastric-type adenocarcinoma in situ (gAIS) and 14 CCCs (13 cervical, 1 vaginal) with these antibodies. We found HNF1β expression in 21 of 23 cases of GAS (91.3%; there was no material available for staining in 1 case), 3/3 cases of gAIS (100%) and 10 of 14 (71.4%) CCCs. Napsin A was expressed in 4 of 24 (16.7%) cases of GAS, 0 of 3 (0%) gAIS, and 11 of 14 (78.6%) CCC. On the basis of these findings, Napsin A is of value in resolving diagnostic confusion between GAS and CCC, whereas HNF1β lacks specificity and its use in this setting is discouraged.

Recent Developments in Non-HPV-related Adenocarcinomas of the Lower Female Genital Tract and Their Precursors.

Most adenocarcinomas in the lower female genital tract (cervix, vagina, vulva) arise in the cervix and are associated with high-risk human papillomavirus (HPV) infection. However, there is an emerging spectrum of non-HPV-related cervical adenocarcinomas, the most common of which is so-called gastric type. In this review, the concept of gastric-type cervical adenocarcinomas and their possible precursor lesions is covered, the precursor lesions still being poorly understood. Other non-HPV-related cervical adenocarcinomas are also discussed, including new information regarding molecular events in mesonephric adenocarcinoma. A variety of primary vaginal adenocarcinomas, including clear cell, endometrioid, intestinal and gastric types are also discussed. The spectrum of benign and malignant glandular lesions involving the lower female genital tract and probably derived from misplaced Skene's (periurethral) glands is also covered.

Outcomes of Definitive Radiation Therapy for Primary Vaginal Carcinoma

The aim of this study was to review treatment and outcomes of patients with primary vaginal cancer treated with definitive radiotherapy. We retrospectively reviewed medical records of 71 patients with primary vaginal adenocarcinoma or squamous cell carcinoma treated with definitive radiotherapy with at least 2 years of follow-up (median follow-up, 6.24 y). Ninety-three percent of patients were treated with external-beam radiotherapy plus brachytherapy (median dose, 7540 cGy); 4 patients with stage I disease and 1 patient with stage II disease were treated with brachytherapy alone (median dose, 6000 cGy). The cause-specific 5- and 10-year survival rates, respectively, were 96% and 96% for stage I patients, 75% and 68% for stage II patients, 69% and 64% for stage III patients, and 53% and 53% for stage IVA patients. The 5- and 10-year local-regional control rates for all patients were 79% and 75%, respectively. The 5- and 10-year distant metastasis-free survival rates for all patients were 87% and 85%, respectively. Sixteen patients had tumors involving the distal one third of the vagina. Of the 7 who received elective inguinal node irradiation, 0 failed in the inguinal nodes. Of the 9 who did not receive elective inguinal node irradiation, 2 failed in the inguinal nodes. Severe complications (grades 3 to 4) occurred in 16 patients (23%). Radiotherapy provides excellent results as definitive treatment for primary vaginal cancer, although the risk of severe complications is high. Generally, treatment should consist of both external-beam radiation therapy and brachytherapy. Inguinal nodes should be irradiated electively when the primary tumor involves the distal one third of the vagina.

Intestinal-type Adenocarcinoma Possibly Arising from a Remnant of the Rectovaginal Fistula Tract Formed after Intermediate-level Imperforate Anus Repair

A 45-year-old Japanese woman, gravid 0, was referred to our hospital with a tentative diagnosis of primary vaginal adenocarcinoma. She complained of mucinous vaginal discharge, intermittent genital bleeding and long-term anal discomfort. She had a history of surgery for intermediate-level imperforate anus in her neonatal period, but we could not get any detailed information about her clinical history because of the loss of her parents in childhood. Pelvic examination revealed an exophytic hemorrhagic tumor filling the vagina. The tumor did not extend into the uterus, and no parametrial tissues or other pelvic organs were involved. She had experienced anal prolapse, which had been recognized about 25 years previously (Fig. 1). Barium enema study exhibited no abnormal findings. Pelvic magnetic resonance imaging studies showed a demarcated tumor 8 4 3 cm in size in a cavity just behind the vagina (Fig. 2, white arrowheads). The tumor filled the vaginal cavity, reaching the introitus (Fig. 2, closed star), but did not contact the rectum (Fig. 2, black asterisk). Positron emission tomography-computed tomography (PET-CT) studies depicted no distant metastasis. Serum carcinoembryonic antigen and sialyl Tn antigen levels were elevated as high as 6.4 ng/ml and 140 U/ml, respectively. The histopathological diagnosis of biopsy specimens was adenocarcinoma. Immunohistochemical staining demonstrated that the tumor tissues were positive for CK7 and CK20. With the preoperative diagnosis of bulky primary adenocarcinoma of the vagina with FIGO stage I and severe anal prolapse, the patient underwent total pelvic exenteration followed by ileal conduit and permanent colostomy. We adopted this procedure including radical hysterectomy with extended total vaginectomy, cystourethrectomy and pelvic lymphadenectomy, firstly, because there is no well-established alternative or adjuvant therapy for vaginal adenocarcinoma and, secondly, because radical hysterectomy with extended total vaginectomy or posterior exenteration frequently denervates the urinary bladder resulting in severe voiding dysfunction. Histopathological diagnosis of the tumor was intestinal-type adenocarcinoma with invasion into the vagina and pelvic adipose tissue. The excisional margin was negative. The tumor was considered to have originated from the intestinal epithelium overlaying a cavity located behind the vagina. The cavity was partly surrounded by muscle layers similar to those of the intestine (Fig. 3). Therefore, we concluded that the tumor had arisen from a remnant of the rectovaginal fistula tract formed 45 years previously after the intermediate-level imperforate anus repair. PET-CT 1 year after the surgery revealed multiple lung metastases. She has been undergoing systemic chemotherapy since then for about 3 years.

Adenocarcinoma Arising from Vaginal Stump

Primary vaginal adenocarcinomas are one of the rarest malignant neoplasms, which develop in the female genital tract. Because of the extremely low incidence, their clinical and pathologic characteristics are still obscure. Recently, we experienced a case of vaginal adenocarcinoma that appeared 7 yr after hysterectomy because of cervical intraepithelial neoplasia. The patient, a 65-yr-old obese woman, was diagnosed as having adenocarcinoma in the vaginal stump and was treated by simple tumor excision and radiation. Immunohistochemical and molecular biologic examinations indicated a potential association with human papilloma virus infection in the development of the vaginal adenocarcinoma. There has been no evidence of recurrence for 3 yr after the operation.

Immunophenotype of Primary Vaginal Adenocarcinoma of MullerianOrigin in a Series of Three Patients

Immunophenotype of Primary Vaginal Adenocarcinoma of MullerianOrigin in a Series of Three Patients

Cutaneous metastasis from primary adenocarcinoma of the vagina: A case report

Cutaneous metastasis in vaginal cancer is an extremely rare event and no cases of cutaneous metastasis from primary vaginal adenocarcinoma have been found. We report the clinicopathologic features, including cytopathologic findings, of the first case of cutaneous metastasis to the anterior chest wall from a sporadic-type advanced primary vaginal adenocarcinoma. Our present case suggested that cytopathologic examination should be performed as soon as possible when a patient exhibits multiple subcutaneous nodules or a painful cutaneous ulcer during treatment of advanced gynecologic cancer.

Primary Vaginal Mucinous Adenocarcinoma of Gastric Type Arising in Adenosis

We report 2 cases of primary vaginal mucinous adenocarcinoma arising in adenosis in nondiethylstilbestrol-exposed women, 1 with uterus didelphys. Both tumors exhibited morphologic and immunohistochemical features (MUC6 and/or HIK 1083 positivity) identical to the recently described cervical gastric-type adenocarcinoma, a subtype of mucinous adenocarcinoma that is non-human papillomavirus related and possibly related to adenoma malignum. Both neoplasms were intensely p53 positive, suggesting that TP53 mutation may be implicated in their development. We believe that the vaginal tumors arose from adenosis through atypical adenosis, as benign and atypical glands were present at the periphery of the neoplasms. In reporting these cases, we discuss atypical adenosis and other types of non-diethylstilbestrol-associated vaginal adenocarcinomas. At least 9 other examples of primary vaginal, or more uncommonly cervical, adenocarcinomas arising in non-diethylstilbestrol-exposed women with congenital genitourinary malformations have been reported, suggesting a probable causal association between congenital malformation, vaginal adenosis, and vaginal adenocarcinoma.

Multimodal therapy in the treatment of vaginal adenocarcinoma arising from endocervicosis

Primary vaginal adenocarcinoma is a rare gynecologicmalignancy. It is thought to arise from vaginal adenosis, endometriosis, embryonic remnants, in-utero DES exposure, or endocervicosis. A computer generated literature search using PubMed and the English search terms “‘primary vaginal adenocarcinoma’ and ‘vaginal endocervicosis’” yielded two cases of vaginal endocervicosis, one associated with a primary non-clear cell vaginal adenocarcinoma [1,2].We report the first case of a metastatic primary vaginal adenocarcinoma thought to arise from malignant transformation of vaginal endocervicosis.

Primary Vaginal Adenocarcinoma Arising in Vaginal Adenosis After CO2 Laser Vaporization and 5-Fluorouracil Therapy

We present a case of a 45-year-old woman with a long-standing history of persistent cervical dysplasia that resulted in a hysterectomy. Subsequent vaginal smears revealed high-grade vaginal intraepithelial neoplasia (VAIN III) on Pap smear with positive human papilloma virus (HPV) testing. Over the course of 2 years, the patient underwent 2 CO(2) laser vaporization procedures of the upper vagina and intermittent 5-fluorouracil therapy. A biopsy performed at the time of the second laser procedure revealed endocervical-type well-differentiated adenocarcinoma, associated with VAIN III. HPV in situ hybridization for HPV types 16 and 18 was positive in both the glandular and squamous mucosa. The patient has no known history of intrauterine diethylstilbestrol exposure or mullerian developmental abnormalities. Subsequently, the patient underwent a radical upper vaginetcomy with bilateral pelvic lymph nodes dissection and bilateral salpingo-oophorectomy. The vaginectomy specimen showed residual adenocarcinoma associated with VAIN-III and extensive vaginal adenosis with free resection margins. This is the second reported case in the literature of adenocarcinoma arising in vaginal adenosis after 5-fluorouracil. Herein, we highlight these important findings and shed some light on the pathogenesis of vaginal adenosis and the subsequent development of vaginal adenocarcinoma.

Primary adenocarcinoma of the vagina successfully treated with neoadjuvant chemotherapy consisting of paclitaxel and carboplatin

Primary vaginal adenocarcinoma unassociated with antenatal diethylstilbestrol (DES) exposure is extremely rare. The strategy for treating this disease has not yet been established due to its rarity and, therefore, the prognosis remains poor. A 69-year-old woman presented with vaginal bleeding but no history of antenatal DES exposure. She had a solid tumor in the recto-vaginal space, diagnosed as FIGO stage III vaginal adenocarcinoma. After neoadjuvant chemotherapy consisting of paclitaxel and carboplatin, the tumor became undetectable. Thereafter, radiotherapy was applied to the pelvis and vagina in order to reinforce the state of remission. The patient remains free from recurrence 1 year after discharge. The present case was successfully treated with chemotherapy and radiotherapy, suggesting that chemotherapy may be an option for the treatment of this type of tumor.

An intravaginal carcinoma tissue in a patient with ovarian tumor

To the Editor, Intravaginal carcinoma tissue appears to be a rare event. The author reports herein an intravaginal foreign body-like carcinoma tissue in a patient with ovarian tumor. A 54-year-old woman was admitted to our hospital because of abnormal genital bleeding. A colposcopic examination revealed a foreign body-like material in the vagina. It was detached easily from the vagina. Clinical cytology was negative for malignancy. During the pathologic examination, the patient underwent imaging modalities including computed tomography and magnetic resonance imaging, which showed a left ovarian tumor. The intravaginal material was submitted to our pathology laboratory. The material measured 6 £ 5 £ 5 mm, and was reddish white and soft. Histologically, it was a carcinoma composed of adenocarcinoma (Fig. 1a) and squamous cell carcinoma (Fig. 1b) elements. The adenocarcinoma element accounted for 60% in area, and the squamous cell carcinoma element 40%. Both elements were admixed, and a gradual transition between them was recognized. The adenocarcinoma element was similar to grade I endometrioid adenocarcinoma, and the squamous element was well diVerentiated squamous cell carcinoma. The gynecologist informed the patient of the presence of carcinoma tissue in the vagina. The patient consulted to another hospital; so the outcome of the patient is unknown for the author. A few possibilities are conceivable. First, the intravaginal carcinoma tissue is a primary adenosquamous cell carcinoma of the vagina. However, this possibility is low because the carcinoma tissue loosely attached to the vaginal walls. Second, the carcinoma tissue is primary vaginal endometrioid adenocarcinoma with malignant squamous

Primary Endometrioid Adenocarcinoma of the Vagina

Vaginal adenocarcinoma is the second most common primary cancer of the vagina, yet there has been very little study of most subtypes other than clear cell carcinoma. We reviewed 18 cases of primary vaginal endometrioid adenocarcinoma, in our experience the second most common subtype. The patients ranged from 45 to 81 years of age (mean 60). Most presented with vaginal bleeding, and had had a prior hysterectomy. Five had a history of unopposed estrogen therapy but none had a history of intrauterine diethylstilbestrol exposure. The tumors were at the vaginal apex in 10 cases, in the posterior wall in 3, the lateral wall in 3, and the anterior wall in 1. On microscopic examination, each of the tumors had a pure or predominant component of typical endometrioid adenocarcinoma. There was squamous metaplasia in 4 cases, mucinous metaplasia in 4, and prominent nonvillous papillae in 2. The tumors were grade 1 of 3 in 4 cases, grade 2 in 13, and grade 3 in 1. Eleven cases were FIGO stage I, 5 stage II, and 2 stage IV. Vaginal endometriosis was identified in 14 cases, and is important in indicating a primary vaginal tumor, rather than secondary spread from the endometrium. Other subtypes of adenocarcinoma (such as serous when the tumor has a papillary pattern) and atypical forms of endometriosis, including polypoid endometriosis, are the most common other differential diagnostic considerations. The prognosis seems to be good in low-stage patients, with 11 patients alive and well and 2 alive with recurrent disease.

Incidental Diagnosis of Primary Vaginal Adenocarcinoma of Intestinal Type

Primary vaginal adenocarcinoma of intestinal type is a rare malignant gynecologic disease. A 53-year-old woman was admitted to our institution with a diagnosis of endometrial adenocarcinoma. A physical examination revealed a 2-cm polypoid lesion of the vagina. The patient underwent surgery for endometrial cancer and wedge resection of the vaginal lesion. The diagnosis of primary vaginal adenocarcinoma of intestinal type was obtained after standard and immunohistochemical analyses of the specimen. No endometrial cancer was detected in the specimen. Radiological investigations excluded metastasis from the gastrointestinal tract. Subsequently, the patient underwent concomitant chemoradiation. At present, 32 months later, she is well and disease-free. Extensive radiological investigations and careful immunohistochemical analysis of the specimen are needed for a correct diagnosis of vaginal adenocarcinoma of intestinal type. Concomitant chemoradiation, as a primary treatment, should be considered.